Abstract: OBJECTIVE： To investigate expression status， clinical implication， and functional role of neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) in esophageal squamous cell carcinoma (ESCC). METHODS： Protein expression of NEDD4 was examined by immunohistochemistry (IHC) in tissue microarrays containing 131 ESCC specimens. Correlations between NEDD4 expression levels and the clinicopathological parameters were analyzed using Pearson Chi- Square and Fisher exact tests. Alterations of NEDD4 mRNA level in ESCC specimens were evaluated using data from the TCGA and GTEx databases. Furthermore， NEDD4 expression was knocked down in ESCC cell lines which had high NEDD4 expressions and changes of cell proliferation activity were detected using the CCK8 assay. RESULTS： Over-expressions of NEDD4 were detected in 40% (53/131) of ESCC specimens，while it was not expressed or expressed at a low level in adjacent normal epithelial tissues. In addition，NEDD4 protein levels were significantly correlated with pathologic T stage and histological grades of ESCC (P < 0.05，respectively). TCGA and GTEX database analysis results show that NEDD4 mRNA levels were also prominently up-regulated in ESCC specimens (P < 0.01). Data of the CCK8 assay further demonstrate that knockdown of NEDD4 expression significantly suppressed the proliferation capacities of KYSE150 and KTSE30 cells in vitro (P < 0.01). CONCLUSION： NEDD4 was frequently up- regulated in ESCC， and its over- expression enhanced proliferation ability of ESCC cells. Our data suggest that abnormal expression of NEDD4 played an oncogenic role in the occurrence and development of ESCC.

Key words: esophageal squamous cell carcinoma, NEDD4, cell proliferation, cancer-promoting effect